Because of its aggressive nature and tendency to relapse, GBM’s five-year survival rates range from 1%–19% with a median survival of only 15 months. GBM is more common (https://www.cancer.org/cancer/brain-spinal-cord-tumors-adults/about/key-statistics.html) in men and those aged 50–70 years.

Presentation and Diagnosis

Patients often present with neurologic symptoms such as headache, vision changes (diplopia or blurred vision), vomiting, mood or personality changes, seizures, and speech changes. Symptoms can be related (https://www.cancer.gov/types/brain/hp) to increased intracranial pressure, swelling, or focal neurologic changes from the tumor size and location in the brain.

Diagnostic workup typically consists of computed tomography (CT) and magnetic resonance imaging (MRI) to identify the extent of disease followed by histologic diagnosis. Tissue biopsy or excision may be added depending on the location of the disease. Intraoperative MRI is sometimes used for image-guided biopsy and tumor removal. Tissue biopsies are analyzed and graded based on aggressiveness and tumor type. The molecular characteristics can affect (https://doi.org/10.1007/s00401-016-1545-1) treatment options and prognosis.

Other prognostic factors include older age, larger tumor size (> 5 cm), tumor crossing midline, neurologic symptoms, and overall functional status. Multifocal GBM will present (https://www.cancer.gov/types/brain/hp) with more than two lesions in about 13% of cases.

Biomarkers

IDH variants, 1p/19q deletion, MGMT promoter methylation, TERT, and EGFRvIII amplification are frequently tested in the diagnosis and prognosis for GBM. When the gene encoding MGMT is turned off by methylation, chemotherapy—specifically temozolomide—may be more effective (https://doi.org/10.1093/neuonc/noy158) because cancer cells cannot repair cellular damage.

Variants in IDH1 or IDH2 genes can confirm that a lesion is a tumor and help diagnose specific subtypes of tumors. Those genes alter the genetic regulation of tumor cells, causing them (https://doi.org/10.1016/j.soncn.2018.10.002) to continue to grow and divide erratically. EGFRvIII amplification highly correlates with glioma subtypes and can be useful in classification. It is found in about 30% of GBM and is associated with more growth-factor signaling and increased numbers of glioma cells.

Alterations in the TERT gene, which enable malignant cells to keep their telomeres long and glioma cells to divide indefinitely without apoptosis, are associated with a poorer prognosis. Gliomas with a BRAF V600E variant may respond to melanoma drugs (e.g., vemurafenib).

Treatment Options

Treatment depends on the location of the disease, and multiple modalities are often used to combat aggressiveness, poor response, and high resistance to therapies. Generally, treatment consists of surgery, postoperative adjuvant radiation, and adjuvant chemotherapy.

Surgery removes as much disease as possible while maintaining neurologic function. Standard external-beam radiation maximizes local control of the excised or biopsied disease. Systemic therapy includes chemotherapy, such as the alkylating agent temozolomide, which can be given (https://www.cancer.gov/types/brain/hp) concurrently with radiation and followed by six or more cycles. Additional surgery, as well as external beam, brachytherapy, gamma knife, or radiosurgery, may be used for some cases of disease recurrence. Treatment response is assessed (https://doi.org/10.1188/16.CJON.S1.2-8) using positron-emission tomography, CT, or MRI. Clinical trials may also be an option for some patients.

Side Effects and Surveillance

Side effects may occur from the disease or its treatment. Neurologic effects can be related extensive surgery or the dose and treatment field for radiation. Other acute side effects from radiation are fatigue, skin changes, and alopecia, and long-term effects involve cognitive changes, endocrine problems, or rare cases of leukoencephalopathy.

Frequently assess for side effects and toxicity from temozolomide, including nausea or vomiting, fatigue, and hematologic effects (e.g., thrombocytopenia, lymphopenia, neutropenia). Consider prophylactic antibiotics for Pneumocystis pneumonia. Routinely conduct laboratory tests, including complete blood counts and liver function, to monitor for severe liver toxicity, which can be fatal. Dose delays and reductions may be indicated.

Patients who present with seizures are treated with antiepileptic drugs, and corticosteroids are often used to reduce disease-related swelling. Assess for side effects (https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Glioblastoma-Multiforme) from long-term corticosteroids, including weight gain, hyperglycemia, insomnia, or myopathy.

Surveillance after primary treatment typically includes MRI approximately four weeks postradiation and at least every two to four months for three years. Implement palliative care early after diagnosis (https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf) to support patients throughout the trajectory of the disease.